The ability to explore, detect and modify the protein features of cell surfaces is a key in the long-term development of many diagnostic and therapeutic strategies. A major obstacle is the fact that the fundamental nature of protein-membrane interactions is largely unknown. Two model systems have been developed for using molecular genetics to determine the principles regulating such interactions: the lysis control genes S of bacteriophage lambda and E of bacteriophage PhiX174. These genes are small (S = 107 codons, E = 91 codons) and lethal, and thus are well-suited for mutational analysis. In vitro mRNA and protein synthesis will be sued to characterize both individually and in pairs representatives from a collection of about 50 missense S mutants in terms of membrane interaction and protease accessibility. Intragenic suppressors of many of these S mutants will be isolated and sequenced to determine interaction domains within the polypeptide. The novel translational control system of S will be probed by site-directed mutagenesis, to determine the parameters by which the two different protein products are synthesized in regulated proportion. The E gene will be subjected to fine structure lac fusion analysis and reversion studies to determine the minimum requirements for membrane insertion of the polypeptide. A missense analysis of the E gene will be carried out in the same way done successfully for the S cistron.